title: Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells.
abstract: Advanced prostate cancers are known to acquire not only invasive capabilities but also significant resistance to chemotherapy-induced apoptosis. To understand how microRNAs (miRNAs) may contribute to prostate cancer resistance to apoptosis, we compared microRNA expression profiles of a benign prostate cancer cell line WPE1-NA22 and a highly malignant WPE1-NB26 cell line (derived from a common lineage). We found that miR-205 and miR-31 are significantly downregulated in WPE1-NB26 cells, as well as in other cell lines representing advanced-stage prostate cancers. Antiapoptotic genes BCL2L2 (encoding Bcl-w) and E2F6 are identified as the targets of miR-205 and miR-31, respectively. By downregulating Bcl-w and E2F6, miR-205 and miR-31 promote chemotherapeutic agents-induced apoptosis in prostate cancer cells. The promoter region of the miR-205 gene was cloned and was found to be hypermethylated in cell lines derived from advanced prostate cancers, contributing to the downregulation of the gene. Treatment with DNA methylation inhibitor 5-aza-2'-deoxycytidine induced miR-205 expression, downregulated Bcl-w, and sensitized prostate cancer cells to chemotherapy-induced apoptosis. Thus, downregulation of miR-205 and miR-31 has an important role in apoptosis resistance in advanced prostate cancer.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, 58108, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bhatnagar
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: S K R
authors.initials: SK
authors.lastname: Padi
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: M-S
authors.initials: MS
authors.lastname: Tang
authors.forename: B
authors.initials: B
authors.lastname: Guo
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D050701:E2F6 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D001374:Azacitidine; D015254:DNA Modification Methylases; D000077209:Decitabine; D050701:E2F6 Transcription Factor; D035683:MicroRNAs; C491073:BCL2L2 protein, human; C491744:E2F6 protein, human; C534425:MIR205, human; C534612:MIRN31 microRNA, human